Effects of Buflomedil and Pentoxifylline on Hamster Skin-Flap Microcirculation: Prediction of Flap Viability Using Orthogonal Polarization Spectral Imaging

OBJECTIVE: This study investigated the effects of buflomedil and pentoxifylline, both of which are used in reconstructive surgery of hamster skin flap microcirculation, and evaluated the skin flap survival rate by orthogonal polarization spectral imaging. METHOD: Twenty-four adult male Syrian golden hamsters were divided into three groups: a control (C, 0.1 ml 0.9% saline), buflomedil (B, 3 mg/kg/day), and pentoxifylline group (P, 14.5 mg/kg/day). Treatments administered intraperitoneally were initiated 1 hour before skin flap preparation and continued for 7 days post-operatively at 12-hour intervals. Preparations (skin flaps) were divided into 12 fields, which were organized into six bands. Functional capillary density (FCD, in mm/mm²), distance from the skin flap base to blood flow cessation (Dist with flow, in cm), percentage of viable skin (VA, in%), and qualitative analysis of blood flow by orthogonal polarization spectral imaging were performed at 1 and 24 hours and on the seventh post-operative day. RESULT: Bands IV, V, and VI presented no flow independent of time. The functional capillary density group B was higher than that of groups C and P, primarily after 24 hours. All groups showed an increase in D with time but reached similar final distances (C = 2.73, B = 2.78 and P = 2.70 cm). Moreover, the percentage of viable areas remained at approximately 50%. The orthogonal polarization spectral imaging was useful to assess viability by counting fields with and without blood flow. CONCLUSIONS: Functional capillary density values were higher in the buflomedil group compared to the control and pentoxifylline groups in this model. Functional capillary density did not influence D or the percentage of VA, and the technique showed favorable potential to assess/predict the viability of skin flaps within 1 h after surgery

Em obesos, a disfunção endotelial correlaciona melhor com a relação cintura-quadril do que com a medida da cintura ou índice de massa corpórea

PURPOSE: Obesity is associated with cardiovascular disease, affecting large arteries and the microcirculation. Waist circumference and body mass index are routinely employed as measures for assessing obesity-related health risk, whereas waist-to-hip ratio is not. We aimed to investigate the association between brachial vascular reactivity and body mass index, waist circumference, and waist-to-hip ratio. METHODS: Eighty-five volunteers (21 men/66 women), aged between 20 and 55 years, underwent determination of waist circumference, body mass index, waist-to-hip ratio, and endothelial function by venous occlusion plethysmography. Forearm blood flow was measured in response to intrabrachial artery infusions of 3 different concentrations of endothelium-dependent (acetylcholine 7.5, 15, and 30 mg/min) and endothelium-independent (sodium nitroprusside 2, 4, and 8 mg/min) vasodilators. RESULTS: There was an inverse correlation of body mass index and waist circumference with forearm blood flow increments after acetylcholine and sodium nitroprusside infusions, while waist-to-hip ratio showed an inverse correlation with forearm blood flow increments only after acetylcholine. When subjects older than 40 years (n = 25) were excluded from the analysis, the inverse correlation of body mass index with forearm blood flow increments after acetylcholine infusion no longer existed, while waist circumference and waist-to-hip ratio showed the same results observed before. CONCLUSION: The waist-to-hip ratio is probably a better estimator of endothelial dysfunction and possibly of cardiovascular risk than body mass index. These findings underscore the importance of routinely collecting hip circumference as an obesity index and risk estimator.OBJETIVO: A obesidade é associada a doenças cardiovasculares e compromete tanto a macro como a microcirculação. As medidas da cintura e do índice de massa corpórea são rotineiramente empregadas para avaliação do risco cardiovascular em obesos, enquanto a relação cintura-quadril é pouco utilizada. O objetivo do trabalho foi determinar que medida antroprométrica, entre as rotineiramente usadas, avalia melhor o risco cardiovascular em obesos. MATERIAL E MÉTODO: Oitenta e quatro voluntários (21 homens/ 66 mulheres), idade entre 20 e 55 anos foram avaliados quanto ao diâmetro da cintura, ao índice de massa corpórea, à relação cintura-quadril e à função endotelial pela técnica de pletismografia com oclusão venosa para medida do fluxo sanguíneo braquial, em resposta a injeção intrabraquial de três doses de acetilcolina (7,5; 15 e 30 mg/min) ou de nitroprussiato de sódio (2; 4 e 8 mg/min), para avaliação da vasodilatação endotélio-dependente e -independente. RESULTADO: Houve correlação inversa entre o índice de massa corpórea, diâmetro da cintura e aumento do fluxo sanguíneo após injeção de acetilcolina e nitroprussiato de sódio, enquanto que a relação cintura-quadril mostrou uma correlação negativa apenas com o aumento no fluxo de sangue no antebraço, após as infusões de acetilcolina. Quando os indivíduos com mais de 40 anos foram retirados da análise, não observamos mais a relação inversa entre índice de massa corpórea e aumento do fluxo sanguíneo após injeção de acetilcolina, enquanto que a cintura e a relação cintura-quadril mantiveram os resultados observados anteriormente. CONCLUSÃO: A relação cintura-quadril é provavelmente um melhor índice para estimar a disfunção endotelial, e consequentemente o risco cardiovascular, que o índice de massa corpórea e esses achados reforçam a importância da aferição da circunferência do quadril como um índice de obesidade e para estimativa do risco cardiovascular

Preconditioning of the response to ischemia/ reperfusion-induced plasma leakage in hamster cheek pouch microcirculation

OBJECTIVE: Ischemic preconditioning and some drugs can protect tissues from injury by preserving microcirculation. This study evaluated vascular permeability in a hamster cheek pouch preparation using either short ischemic periods or bradykinin as preconditioning stimuli followed by 30 min of ischemia/reperfusion. METHOD: Sixty-six male hamsters were divided into 11 groups: five combinations of different ischemic frequencies and durations (one, three or five shorts periods of ischemia, separated by one or five minutes) with 10 min intervals between the ischemic periods, followed by 30 min ischemia/reperfusion; three or five 1 min ischemic periods with 10 min intervals between them followed by the topical application of histamine (2 µM); bradykinin (400 nM) followed by 30 min of ischemia/reperfusion; and three control groups (30 min of ischemia/reperfusion or histamine or bradykinin by themselves). Macromolecular permeability was assessed by injection of fluorescein-labeled dextran (FITC-dextran, MW= 150 kDa; 250 mg/Kg body weight), and the number of leaks/cm2 was counted using an intravital microscope and fluorescent light in the cheek pouch. RESULTS: Plasma leakage (number of leaks/cm²) was significantly reduced by preconditioning with three and five 1 min ischemic periods, one and three 5 min ischemic periods and by bradykinin. Histamine-induced macromolecular permeability was also reduced after three periods of 5 min of ischemia. CONCLUSION: Short ischemic periods and bradykinin can function as preconditioning stimuli of the ischemia/reperfusion response in the hamster cheek pouch microcirculation. Short ischemic periods also reduced histamineinduced macromolecular permeability

Relação entre as adipocinas, inflamação e reatividade vascular em controles magros e pacientes obesos com síndrome metabólica

PURPOSE: Metabolic syndrome is an important risk factor for cardiovascular disease. Adipokines interfere with insulin action and endothelial cell function. We investigated the relationship among adipokines, metabolic factors, inflammatory markers, and vascular reactivity in obese subjects with metabolic syndrome and lean controls. METHODS: Cross-sectional study of 19 obese subjects with metabolic syndrome and 8 lean volunteers evaluated as controls. Vascular reactivity was assessed by venous occlusion pletysmography measuring braquial forearm blood flow (FBF) and vascular resistance (VR) responses to intra-arterial infusions of endothelium-dependent (acetylcholine-Ach) and independent (sodium nitroprusside-SNP) vasodilators. Blood samples were obtained to evaluate C reactive protein (CRP), plasminogen activator inhibitor 1 (PAI-1), fibrinogen, adiponectin, resistin, and lipid profile. Patients were classified with regard to insulin resistance through the HOMA-IR index. RESULTS: PAI-1, CRP and fibrinogen were higher and adiponectin was lower in metabolic syndrome subjects compared to controls. Metabolic syndrome subjects had impaired vascular reactivity. Adiponectin and PAI-1 were associated with insulin, HOMA-IR, triglycerides, and HDLc; and resistin with CRP. Adiponectin was associated with VR after Ach in the pooled group and resistin with D FBF after Ach in the metabolic syndrome group. CONCLUSION: Metabolic syndrome subjects exhibited low levels of adiponectin and high levels of CRP, fibrinogen, and PAI-1. Adiponectin and PAI-1 correlated with insulin resistance markers. Adiponectin and resistin correlated with vascular reactivity parameters. An adipocyte-endothelium interaction might be an important mechanism of inflammation and vascular dysfunction.A Síndrome Metabólica é um importante fator de risco para doenças cardiovasculares. As adipocinas interferem com a ação da insulina e com a função endotelial. OBJETIVO: Investigar a relação entre adipocinas, fatores metabólicos, marcadores inflamatórios e reatividade vascular para inferência da função endotelial em pacientes obesos e controles magros. MATERIAL E MÉTODO: Estudo transversal de 19 pacientes obesos com Síndrome Metabólica e 8 controles magros. A reatividade vascular foi avaliada pela pletismografia de oclusão venosa medindo o fluxo sangüíneo da artéria braquial e sua resistência vascular a partir de infusões intra-arteriais de vasodilatadores endotélio-dependente (acetilcolina) e endotélio-independente (nitroprussiato de sódio). Foram também avaliados no sangue a proteína C reativa (PCR), o inibidor do ativador do plasminogênio 1 (PAI-1), fibrinogênio, adiponectina, resistina e o perfil lipídico. Os pacientes foram classificados quanto à resistência insulínica pelo índice HOMA-IR. RESULTADO: PAI-1, PCR e fibrinogênio apresentaram valores mais altos e a adiponectina mais baixos para os pacientes com Síndrome Metabólica do que com os controles. Pacientes com Síndrome Metabólica apresentaram prejuízo da reatividade vascular. A adiponectina e PAI-1 estiveram associadas à insulina, HOMA-IR, triglicerídeos e HDLc; e resistina com o PCR. Adiponectina esteve associada com a resistência vascular e a resistina com o fluxo sangüíneo depois da acetilcolina em pacientes com Síndrome Metabólica. CONCLUSÃO: Pacientes com Síndrome Metabólica exibiram baixas concentrações sangüíneas de adiponectina e altos níveis de PCR, fibrinogênio e PAI-1. Adiponectina e PAI-1 correlacionaram com os marcadores da resistência insulínica. Adiponectina e resistina correlacionaram com a reatividade vascular. A interação adipócito-endotélio vascular pode ser um importante mecanismo de inflamação e disfunção vascular

Effects of moderate and high intensity isocaloric aerobic training upon microvascular reactivity and myocardial oxidative stress in rats

Peer reviewedPublisher PD

Treatment of Essential Hypertension does not Normalize Capillary Rarefaction

OBJECTIVES: To determine if capillary rarefaction persists when hypertension is treated with angiotensin converting enzyme inhibitor, thiazidic diuretic and/or beta-blocker, and to identify which microcirculatory alterations (structural and functional) persist after anti-hypertensive treatment. METHODS: We evaluated 28 well-controlled essential hypertensive patients and 19 normotensive subjects. Nailfold videocapillaroscopy examination of the fourth finger of the left hand was used to determine the functional capillary densities at baseline, during post-occlusive hyperemia, and after venous congestion. Capillary loop diameters (afferent, apical and efferent) and red blood cell velocity were also quantified. RESULTS: Compared with normotensive subjects, hypertensive patients showed lower mean functional capillary density at baseline (25.1±1.4 vs. 33.9±1.9 cap/mm², p<0.01), during post-occlusive reactive hyperemia (29.3±1.9 vs. 38.2±2.2 cap/mm², p<0.01) and during venous congestion responses (31.4±1.9 vs. 41.1±2.3 cap/mm², p<0.01). Based on the density during venous congestion, the estimated structural capillary deficit was 25.1%. Mean capillary diameters were not different at the three local points, but red blood cell velocity at baseline was significantly lower in the hypertensive group (0.98±0.05 vs. 1.17±0.04 mm/s, p<0.05). CONCLUSIONS: Patients treated for essential hypertension showed microvascular rarefaction, regardless of the type of therapy used. In addition, the reduced red blood cell velocity associated with capillary rarefaction might reflect the increased systemic vascular resistance, which is a hallmark of hypertension

Evaluation of sublingual microcirculation in children with dengue shock

OBJECTIVE: To report the sublingual microcirculation observed using Sidestream Dark Field imaging in two children with dengue shock. METHOD: Two children, aged 9 and 10 years, were admitted to the pediatric intensive care unit with dengue shock and multiple organ dysfunction. Sublingual microcirculation was assessed in each patient on the first and second days of shock and was assessed a final time when the patients were no longer in shock (on the day prior to extubation) using Sidestream Dark Field technology. The De Backer score and microvascular flow index were used for the analyses. RESULTS: Both patients had reduced perfused small vessel density in the first two days and showed predominantly intermittent or no microcirculation flow, as demonstrated by a low microvascular flow index. The blood flow in the large vessels was not affected. Prior to the extubation, the microvascular flow index had increased, although the perfused small vessel density remained diminished, suggesting persistent endothelial dysfunction. CONCLUSIONS: Severe microcirculation changes may be involved in the pathophysiological mechanisms that lead to the final stages of dengue shock, which is frequently irreversible and associated with high mortality rates. Microcirculatory monitoring may help elucidate the physiopathology of dengue shock and prove useful as a prognostic tool or therapeutic target

The endothelium in the metabolic syndrome

The endothelium is responsible for the maintenance of vascular homeostasis. In physiological conditions it acts keeping vascular tonus, laminar blood flow, plasmatic membrane fluidity, the balance between coagulation and fibrinolysis and the inhibition of cellular proliferation, migration and the inflammatory response. Endothelial dysfunction is defined as an alteration of vascular relaxation induced by reduction of endothelium-derived relaxing factors (ERRFs), mainly nitric oxide. These abnormal vasomotor responses occur in the presence of various risk factors for atherosclerosis. The metabolic syndrome is considered a state of chronic inflammation accompanied of endothelial dysfunction causing an increased incidence of ischemic cardiovascular events and high mortality. This revision will encompass the physiological process of vascular function regulation, methods for in vivo assessment of endothelial dysfunction and therapies capable to improve vascular function and consequently minimize the cardiovascular risk due to metabolic syndrome.O endotélio é responsável pela manutenção da homeostase vascular. Em condições fisiológicas, mantém o tônus vascular, o fluxo sangüíneo laminar, a fluidez da membrana plasmática, o equilíbrio entre coagulação e fibrinólise, a inibição da proliferação e da migração celulares e o controle da resposta inflamatória. A disfunção endotelial é definida como uma alteração do relaxamento vascular por diminuição da biodisponibilidade de fatores de relaxamento derivados do endotélio, principalmente o óxido nítrico (NO). Estas respostas vasomotoras anormais ocorrem na presença de inúmeros fatores de risco para a aterosclerose. A síndrome metabólica é considerada um estado de inflamação crônica que se acompanha de disfunção endotelial e ocasiona aumento na incidência de eventos isquêmicos cardiovasculares e elevada mortalidade. Essa revisão abordará o processo fisiológico de regulação da função vascular pelo endotélio, os métodos disponíveis para avaliação in vivo da disfunção endotelial e as terapias capazes de melhorar a função vascular e conseqüentemente minimizar o risco cardiovascular dessa síndrome tão prevalente no nosso meio.29130

Enhancing identification and treatment of patients with concomitant chronic venous insufficiency and diabetes mellitus A modified Delphi study from the CODAC (ChrOnic venous disease and Diabetes Advisory Council) group

Background: Chronic venous insufficiency (CVI) and diabetes mellitus (DM) pose significant burdens to patients and healthcare systems. While the two diseases share a number of commonalities in risk factors and pathophysiology, they are often assessed and managed separately. This can lead to a worsening of comorbidities and limitations in a patient’s quality of life. This project aims to develop recommendations to enhance the identification and treatment of patients with concomitant CVI and DM. Methods: Using a modified Delphi method, a panel of experts developed 38 Likert Scale and two multiple choice questions across six key themes. These were used to form an online survey which was disseminated through a convenience sampling approach to CVI and DM healthcare professionals across Europe, Central America, South America, and the Middle East. The threshold for consensus was set at ≥75%.Results: A total of 238 responses were received. 27/38 statements attained &gt;90% agreement, nine of 38 attained between 75-90%, and two failed to meet the threshold (&lt;75%). The awareness around the impact of the two diseases was high, but a gap was highlighted in the identification of patients with concomitant CVI and DM. Conclusions: The high level of agreement shows that healthcare professionals are aware of the gaps in identification and treatment of patients with concomitant CVI and DM, and of the need to approach this as a combined therapy area. An algorithm is proposed to help the identification of at-risk patients and to provide recommendations on the management of patients with concomitant disease. (Cite this article as: Bozkurt AK, van Rijn MJ, Bouskela E, Gastaldi G, Glauser F, Haller H, et al. Enhancing identification and treatment of patients with concomitant chronic venous insufficiency and diabetes mellitus. A modified Delphi study from the CODAC (ChrOnic venous disease and Diabetes Advisory Council) group. Int Angiol 2023;42:427-35. DOI: 10.23736/S0392-9590.23.05061-7)</p

The OpenModelica integrated environment for modeling, simulation, and model-based development

OpenModelica is a unique large-scale integrated open-source Modelica- and FMI-based modeling, simulation, optimization, model-based analysis and development environment. Moreover, the OpenModelica environment provides a number of facilities such as debugging; optimization; visualization and 3D animation; web-based model editing and simulation; scripting from Modelica, Python, Julia, and Matlab; efficient simulation and co-simulation of FMI-based models; compilation for embedded systems; Modelica- UML integration; requirement verification; and generation of parallel code for multi-core architectures. The environment is based on the equation-based object-oriented Modelica language and currently uses the MetaModelica extended version of Modelica for its model compiler implementation. This overview paper gives an up-to-date description of the capabilities of the system, short overviews of used open source symbolic and numeric algorithms with pointers to published literature, tool integration aspects, some lessons learned, and the main vision behind its development.Fil: Fritzson, Peter. Linköping University; SueciaFil: Pop, Adrian. Linköping University; SueciaFil: Abdelhak, Karim. Fachhochschule Bielefeld; AlemaniaFil: Asghar, Adeel. Linköping University; SueciaFil: Bachmann, Bernhard. Fachhochschule Bielefeld; AlemaniaFil: Braun, Willi. Fachhochschule Bielefeld; AlemaniaFil: Bouskela, Daniel. Electricité de France; FranciaFil: Braun, Robert. Linköping University; SueciaFil: Buffoni, Lena. Linköping University; SueciaFil: Casella, Francesco. Politecnico di Milano; ItaliaFil: Castro, Rodrigo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Investigación en Ciencias de la Computación. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Investigación en Ciencias de la Computación; ArgentinaFil: Franke, Rüdiger. Abb Group; AlemaniaFil: Fritzson, Dag. Linköping University; SueciaFil: Gebremedhin, Mahder. Linköping University; SueciaFil: Heuermann, Andreas. Linköping University; SueciaFil: Lie, Bernt. University of South-Eastern Norway; NoruegaFil: Mengist, Alachew. Linköping University; SueciaFil: Mikelsons, Lars. Linköping University; SueciaFil: Moudgalya, Kannan. Indian Institute Of Technology Bombay; IndiaFil: Ochel, Lennart. Linköping University; SueciaFil: Palanisamy, Arunkumar. Linköping University; SueciaFil: Ruge, Vitalij. Fachhochschule Bielefeld; AlemaniaFil: Schamai, Wladimir. Danfoss Power Solutions GmbH & Co; AlemaniaFil: Sjolund, Martin. Linköping University; SueciaFil: Thiele, Bernhard. Linköping University; SueciaFil: Tinnerholm, John. Linköping University; SueciaFil: Ostlund, Per. Linköping University; Sueci